Randomized Phase II Trial of Onartuzumab in Combination With Erlotinib in Patients With Advanced Non–Small-Cell Lung Cancer
| Autor: | Jiping Zha, Rodryg Ramlau, J. Goldschmidt, David R. Spigel, Maciej Krzakowski, Benoit Godbert, Gilles Robinet, Michael S. Wertheim, George R. Blumenschein, Thomas Ervin, Robert L. Yauch, Premal Patel, Fabrice Barlesi, Ramaswamy Govindan, Wei Yu, Sergey Orlov, Amy C. Peterson, Taral Patel, See Chun Phan, Davey B. Daniel |
|---|---|
| Rok vydání: | 2013 |
| Předmět: |
Oncology
Cancer Research medicine.medical_specialty education.field_of_study biology business.industry Population Hazard ratio Cancer medicine.disease Surgery Onartuzumab Internal medicine biology.protein medicine Epidermal growth factor receptor Erlotinib Lung cancer education Erlotinib Hydrochloride business medicine.drug |
| Zdroj: | Journal of Clinical Oncology. 31:4105-4114 |
| ISSN: | 1527-7755 0732-183X |
| DOI: | 10.1200/jco.2012.47.4189 |
| Popis: | Purpose Increased hepatocyte growth factor/MET signaling is associated with poor prognosis and acquired resistance to epidermal growth factor receptor (EGFR) –targeted drugs in patients with non–small-cell lung cancer (NSCLC). We investigated whether dual inhibition of MET/EGFR results in clinical benefit in patients with NSCLC. Patients and Methods Patients with recurrent NSCLC were randomly assigned at a ratio of one to one to receive onartuzumab plus erlotinib or placebo plus erlotinib; crossover was allowed at progression. Tumor tissue was required to assess MET status by immunohistochemistry (IHC). Coprimary end points were progression-free survival (PFS) in the intent-to-treat (ITT) and MET-positive (MET IHC diagnostic positive) populations; additional end points included overall survival (OS), objective response rate, and safety. Results There was no improvement in PFS or OS in the ITT population (n = 137; PFS hazard ratio [HR], 1.09; P = .69; OS HR, 0.80; P = .34). MET-positive patients (n = 66) treated with erlotinib plus onartuzumab showed improvement in both PFS (HR, .53; P = .04) and OS (HR, .37; P = .002). Conversely, clinical outcomes were worse in MET-negative patients treated with onartuzumab plus erlotinib (n = 62; PFS HR, 1.82; P = .05; OS HR, 1.78; P = .16). MET-positive control patients had worse outcomes versus MET-negative control patients (n = 62; PFS HR, 1.71; P = .06; OS HR, 2.61; P = .004). Incidence of peripheral edema was increased in onartuzumab-treated patients. Conclusion Onartuzumab plus erlotinib was associated with improved PFS and OS in the MET-positive population. These results combined with the worse outcomes observed in MET-negative patients treated with onartuzumab highlight the importance of diagnostic testing in drug development. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|